The cytotoxic drugs cyclophosphamide (CPO) and ifosfamide (IFO) cause toxic urological effects due to the production of urinary metabolites that cause bladder inflammation. This study aimed to identify changes in the bladder afferent system following treatment with these drugs that might explain reported urological adverse effects. Intravesical pressure and afferent nerve activity were recorded during bladder distension and drug administration in isolated bladders from mice, 24 h after intraperitoneal treatment with cyclophosphamide (100 mg/kg), ifosphamide (200 mg/kg) or saline (control). In isolated bladders, total afferent nerve activity at maximum bladder distension was increased from 182 ± 13 imp/s in control animals, to 230 ± 14 imp/s in CPO-treated (p < 0.05) and 226 ± 17 imp/s in IFO-treated (p < 0.001) mice. Single fibre analysis revealed the increase resulted from an enhanced activity in low threshold, wide dynamic range fibres (23.3 ± 1.9 imp/s/fibre in controls to 31.5 ± 2.5 (p < 0.01) in CPO and 29.9 ± 2.0 imp/s/fibre (p < 0.05) in IFO treated). CPO treatment was accompanied by an increase in urinary frequency in vivo, but was not associated with increases in urothelial release of ATP or acetylcholine, bladder compliance or spontaneous muscle activity. Also, CPO-treatment did not affect afferent nerve responses or pressure responses to purinergic, muscarinic or nicotinic agonists. This is the first report of CPO and IFO-induced changes in specific populations of bladder afferents, namely an increase in low threshold, wide dynamic range fibres. These effects appear to be direct and not secondary to increases in smooth muscle activity or the release of urothelial mediators.

中文翻译：

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膀胱超敏反应的阈值低，动态范围宽，经化疗药物环磷酰胺和异环磷酰胺治疗后的传入纤维。

细胞毒性药物环磷酰胺（CPO）和异环磷酰胺（IFO）由于产生会引起膀胱炎症的尿代谢物而引起毒性泌尿学作用。这项研究旨在确定用这些药物治疗后膀胱传入系统的变化，这可能解释了所报告的泌尿外科不良反应。腹膜内用环磷酰胺（100 mg / kg），异环磷酰胺（200 mg / kg）或生理盐水（对照组）腹膜内处理后24小时，在小鼠离体的膀胱中记录膀胱扩张和给药期间的膀胱内压力和传入神经活动。在孤立的膀胱中，最大膀胱扩张时的总传入神经活动从对照组动物的182±13 imp / s增加到CPO治疗组的230±14 imp / s（p <0.05）和IFO的226±17 imp / s -治疗（p ＜0.001）的小鼠。单纤维分析显示，增加的增加是由于低阈值，宽动态范围的纤维（对照中的23.3±1.9 imp / s /纤维至CPO中的31.5±2.5（p <0.01）和29.9±2.0 imp / s /纤维）的增强的活性所致（p <0.05）在IFO中）。CPO治疗伴随着体内尿频的增加，但与尿路上皮ATP或乙酰胆碱释放，膀胱顺应性或自发肌肉活动的增加无关。而且，CPO处理不影响嘌呤能，毒蕈碱或烟碱激动剂的传入神经反应或压力反应。这是CPO和IFO引起的特定的膀胱传入人口变化（即低阈值，宽动态范围纤维增加）的首次报道。